Zinc Status in Virological Controlled Human Immunodeficiency Virus Type 1 Infected Patients

doi:10.4236/wja.2011.14026

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World Journal of AIDS, 2011, 1, 182-184

doi:10.4236/wja.2011.14026 Published Online December 2011 (http://www.SciRP.org/journal/wja)

Zinc Status in Virological Controlled Human

Immunodeficiency Virus Type 1 Infected

Patients

Carlos Tornero, Consuelo Lapuebla, Ana Ventura, Julian Diaz, Maricarmen Mafe

Internal Medicine Department and Laboratory, Hospital Gandia, Valencia, Spain.

E-mail: [email protected]

Received August 1st, 2011; revised September 12th, 2011; accepted September 24th, 2011.

ABSTRACT

Zinc (Zn) is a key micronutrient for correct immune function and its deficiency correction has been shown to be useful

in HIV-infected but most of the studies included a significant proportion of patients without adequate virological con-

trol. It would be interesting to establish the prevalence, associated factors and clinical repercussions of Zn deficiency in

patients with good virological to assessing the usefulness of Zn monitoring in the routine follow-up of well controlled

HIV-infected patients, based on the colorimetric techniques commonly used in daily clinical practice. We included the

first 100 patients that met the requirements of HAART and viremia levels under 200 copies for at least 6 consecutive

months, with no active illicit drug use, active infections or weight loss of any cause during the previous 6 months. Se-

rum Zn concentration was measured using a colorimetric assay (Sentinel Diagnostics®) adapted to the Cobas 8000

analyzer (Roche Diagnostics). The Zn values showed a normal distribution with a mean concentration of 88.7 µg/dl

(SD 23.3) and were found to b e decreased in 13 patients and in 6 subjects were below 61 µg/dl. Both the simple statis-

tical analysis and the multivariate regression model only identified a significant effect for age and alcoho l consumption.

In sum an important number of HIV-infected with effective and prolonged HAART and no evidence of active infections

or other associated factor show diminished serum Zn concentrations. The inclusion of at least occasional Zn determi-

nations should be considered in the regular follow-up evaluations of HIV-infected patients.

Keywords: Zinc, Micronutrients, HAART

1. Introduction

Zinc (Zn) is a key micronutrient for correct immune

function. Zinc deficiency is not uncommon, and its cor-

rection has been shown to be useful in a number of clini-

cal contexts [1]. HIV-infected patients often present Zn

deficiency, and normalization of the levels of this ele-

ment likewise offers benefit for such individuals [2].

However, most of the studies conducted in these subjects

were published before highly active antiretoviral therapy

(HAART) were available, and included a significant

proportion of patients without adequate virological con-

trol, illicit drug users, and patients with active infections

or malnutrition of different origins. It would be interest-

ing to establish the prevalence, associated factors and

clinical repercussions of Zn deficiency in patients with

good virological control and without the aforementioned

factors, with a view to assessing the usefulness of Zn

monitoring in the routine follow-up of well controlled

HIV-infected patients, based on the colorimetric tech-

niques commonly used in daily clinical practice.

2. Material and Methods

The systematic determination of Zn was introduced in all

patients followed-up on in a center specialized in the

management of HIV-infected individuals. We included

the first 100 patients that met the requirements of

HAART and viremia levels under 200 copies for at least

6 consecutive months, with no active illicit drug use,

active infections or weight loss of any cause during the

previous 6 months. Anthropometric data were collected,

together with information relating to alcohol consump-

tion, the presence of diarrhea, lipodystrophy, skin lesions,

nadir and present CD4+ lymphocytes counts, transami-

nases levels and antecedents of decompensated liver cir-

rhosis. A total of 13 4 patients were seen until the planned

00 subjects were recruited (Table 1). 1

Zinc Status in Virological Controlled Human Immunodeficiency Virus Type 1 Infected Patients183

Table 1. Baseline characteristics.

Age, mean years ± SD 44.5 ± 10.05

Sex, % males 64

CD4 cell count, mean years ± SD

Nadir 218.1 ± 172.1

Current 640 ± 357

Alcohol use % participans 13

BMI, mean kg/m2 ± SD 25.3 ± 4.6

Receiving ART and with undetectable viral load (<200 copies/mL) 100%

Serum zinc levels mean mcgr/dl , mean ± SD 88.7 ± 23.3

Serum Zn concentration was measured using a colori-

assay (Sentinel Diagno stics®) adapted to the Cobas 8000

analyzer (Roche Diagnostics). The adult serum reference

values were 66 - 150 µg/dl. The SPSS version 13.0 sta-

tistical package was used to analyze the results, based on

the Student t-test and Mann-Whitney U-test for categ ori-

cal variables and using the Pearson correlation coeffi-

cient for quantitative variables. For the multivariate

analysis we constructed a multivariate regression model

with the Zn concen tratio ns as response variable.

3. Results

The Zn values showed a normal distribution with a mean

concentration of 88.7 µg/dl (SD 23.3). The levels were

found to be decreased in 13 patients (13%; 95% CI 6 -

19), and in 6 subjects were below 61 µg/dl. Both the

simple statistical analysis and the multivariate regression

model only identified a significant effect (R: 0.114, p <

0.01) for age (Cr : 0.15 ; 95% CI 0.04 - 0.25 , p < 0.01) an d

alcohol consumption (Cr: 14.67 ; 95%CI 1.49 - 27.85, p =

0.03), no differences being observed with respect to the

nadir CD4+ lymphocytes count, present CD4+ lympho-

cytes count, body mass index, presence of diarrhea, li-

podystrophy, transaminase elevation or diagnosis of liver

cirrhosis. Zinc replacement therapy or dietary recom-

mendations were provided in these subjects.

4. Comments

Zinc is a microelement obtained mainly from meat and

legumes, and is absorbed in the jejunum and to a lesser

extent in the large bowel, in relation to the plasma levels

reached. Pancreatic enzyme alterations and diarrhea re-

duce Zn absorp tion, though the levels of this element are

also found to be decreased in acute inflammatory proc-

esses, nutritional deficiencies, alcoholism, chronic liver

disease and in intravenous drug abusers [1]. In view of

the relationship between Zn and correct immune function,

this element has been extensively studied in HIV-in-

fected individuals, where Zn deficiency is common—

probably due to a coincidence of many of the above

mentioned factors: lack of control of the infection [3],

nutritional deficiency particularly in intravenous drug

abusers [4], alcoholism and terminal liver diseases [5],

diarrhea [3], etc. In turn, Zn deficiency in HIV-infected

patients has been associated to increased viral replication

and a poorer diag nosis [3,6], and correction of such defi-

ciency has been correlated to improvements in survival

and immune recovery [3,6-8].

Studies in the HAART era have reported Zn defi-

ciency in over 30% of all patients, with immunological

benefits once the problem is corrected. However, in these

studies the percentage of patients with virological control

and the absence of other confounding factors is low [3,9].

The interest of our study is that it involves a group of

patients with effective and prolonged HAART and no

evidence of active infections or other associated factors,

in which the Zn deficiency rate was found to be 13% -

with severe deficiency in 6%. Among the mentioned

factors associated to Zn deficiency, only at least moder-

ate alcohol consumption was associated to diminished

levels of the element—no correlation being observed

with transaminase elevation, liver cirrhosis, lipodystro-

phy, diarrhea or CD4+ counts. Although we cannot rule

out specific nutritional deficiencies, the latter were not

clinically evident, since we did not include patients with

recent weight loss, and the body mass index of the sub-

jects with Zn deficiency was 25.3 kg/m2 (SD 4.6). In

contrast, we observed an inverse correlation to age not

previously d e scribed in the literature, and which might be

attributable to dietary differences. Possibly other factors,

e.g., non-evident active infections such as hepatitis C,

persistent immune activation phenomena inherent to HIV

disease, or dietary or genetic factors co nditioning absorp-

tion could explain some case of Zn deficiency [10]. The

direct colorimetric method used in this study offers the

advantages of being technically easier, automatically

Zinc Status in Virological Controlled Human Immunodeficiency Virus Type 1 Infected Patients

184

performed and less costly than the atomic absorption

spectrophotometric techniques used in other studies, and

as such is the method usually employed in clinical labo-

ratories. As has been commented, the clinical relevance

of Zn deficiency and the benefits derived from correcting

the problem are difficult to establish in our case, because

most of the patients had high CD4+ counts (640

cells/mm3, SD 357)—with no differences versus patients

without Zn deficiency.

In sum, an important number of HIV-infected patients

in the HAART era show diminished serum Zn concentra-

tions. In a large percentage of cases the underlying cause

cannot be identified, since these subjects have good vi-

rological control, with no liver disease or malnutrition.

Further studies are needed to establish the causes and

corroborate the usefulness of Zn replacement therapy—

though given the high prevalence of Zn deficiency even

in patients with good nutritional status and virological

control, the inclusion of at least occasional Zn determi-

nations should be considered in the regular follow-up

evaluations of HIV-infected patients.

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